Myelodysplastic syndrome in children and adolescents

Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and subsequent frequent development of acute myeloid leukemia (AML). In children and adolescents, MDS are uncommon disorders, accounting for less than 5% of hematopoietic malignancy, with great heterogeneity in presentation and clinical course. The genetic changes predisposing children to MDS are largely obscure. Monosomy 7 is the most common chromosomal abnormality, often occurring as a sole abnormality. The recent pediatric modification of the World Health Organization (WHO) classification has greatly facilitated the diagnostic process. Refractory cytopenia (RC) is the most common MDS subtype in children, occurring in about half of all MDS cases. There is consensus that the relationship between MDS with increased blast count and de novo AML is better defined by biological and clinical features than by blast count. Because monosomy 7 is the only chromosomal abnormality strongly suggestive of MDS, children presenting with a low blast count and other chromosomal aberrations or normal karyotype must be closely observed before a diagnosis of MDS can be established. With an increasing number of children surviving primary cancer with chemotherapy or radiation therapy, the incidence of secondary therapy-related MDS is rising. The MDS risk is also increased in patients with inherited bone marrow failure disorders; this relationship provides valuable insights into MDS biology. Allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related or suitable unrelated donor is the choice for most children with MDS and can rescue a large proportion of patients.